Synthesis, Characterization and Application of Novel Palladium Complexes

Abstract

Palladium(II)thiosemicarbazone complexes are known to be good anticancer agents. However, their stability is a challenge during biological application because of faster ligand exchange kinetics. This research focused on synthesis of palladium complexes with bulky ligands to improve their stability. Thiosemicarbazone (TSC) ligands were synthesized via condensation reaction of aldehydes and respective amines. The following ligands were synthesized; (E)-N,N’-dimethyl-2-((5’-methyl-[2,2’-bithiophen]-5-yl)methylene)hydrazine-1-carbothioamide (L1), (E)-N-ethyl-2-((5-phenylthiophen-2-yl)methylene)hydrazine-1-carbothioamide (L2)and (E)-2-((5’methyl)-[2,2’-bithiophen]-5-yl)methylene)-N-phenylhydrazine-1-carbothioamide (L3). Corresponding Pd(II) complexes were synthesized by reacting equimolar amounts of ligands and Pd(cod)Cl2. Complexes synthesized were; (E)-N,N’-dimethyl-2-((5’-methyl-[2,2’-bithiophen]-5-yl)methylene)hydrazine-1-carbothioamide palladium(II)chloride complex (C1), (E)-N-ethyl-2-((5-phenylthiophen-2-yl)methylene)hydrazine-1-carbothioamide palladium(II)chloride complex (C2) and (E)-2-((5’methyl)-[2,2’-bithiophen]-5-yl)methylene)-N-phenylhydrazine-1-carbothioamide palladium(II)chloride complex (C3).Stability test for ligands and complexes were done using 1HNMR in DMSO-d6 within a period of 72 hours at an interval of 6 hours monitoring any peak change. Both ligands and complexes were characterized by UV-Vis, FTIR, 1H NMR, 13C NMR, elemental analysis and single crystal X-ray diffraction for L2. Single crystal X-ray crystallography revealed that the prepared ligand had E conformationand existed as thione tautomer. Elemental analysis result indicated that L1 and L2 coordinated to palladium metal in N S bidentate fashion while L3 in SNS tridentate fashion. UV-Vis studies were done on ligand to confirm formation of imine around 300nm (π→π* transition). UV-Visalso revealed Ligand to metal charge transfer (LMCT) transition confirmed successful coordination of ligands through S-M bond. The anticancer activities of ligands and complexes were screened against Caco-2, HT-29, HeLa and KMST cell lines using cisplatin as a positive control. The ligands displayed low anticancer potency compared to corresponding complexes except for L1. L3 had the lowest inhibition to all cell lines with IC50> 100 μg/mL.However after complex formation, C3 showed inhibition; Caco-2 (IC50=84.32 μg/mL), HT-29 (IC50=49.10 μg/mL), HeLa (IC50=0.73 μg/mL) and KMST (IC50>100 μg/mL). All the cell lines displayed high susceptibility to L1; Caco-2 (IC50=6.814 μg/mL), HT-29 (IC50=6.449 μg/mL), HeLa (IC50=0.2619 μg/mL) and KMST (IC50=10.7900 μg/mL). Among the ligands and complexes C3 had selective anticancer properties. Caco-2 cell displayed some resistance to inhibition to all the compounds.The complexes had enhanced anticancer activities compared with the respective ligands except for L1. Synthesized palladium(II) complexes with bulky ligands were stable and were cytotoxic towards cancer cell lines.